Two discrete regions of deletion at 7q in uterine leiomyomas

Abstract

This study further defines the region of consistent deletion of chromosome 7 in uterine leiomyomas. We have examined 74 leiomyomas for allelic loss of markers spanning the 7q22 region defined by markers D7S518 and D7S471. Forty tumors with cytogenetically defined 7q deletions, twenty‐nine tumors without cytogenetically visible 7q deletions, and five tumors with no cytogenetic information were examined for allelic loss of D7S518, D7S666, D7S515, D7S658, D7S496, D7S692, and D7S471. Loss of heterozygosity for one or more of these loci was observed in twenty‐eight leiomyomas with cytogenetically defined 7q deletions and in three leiomyomas with a normal karyotype. Allelic loss of D7S666 was common and was observed in all twenty‐three informative tumors with 7q deletions and in two tumors with normal karyotypes. This study indicates the presence of a tumor suppressor gene in close proximity to the D7S666 locus. Eight tumors followed an unusual pattern of allelic loss. These tumors showed retention of heterozygosity for at least one locus flanked by deleted loci. These results suggest the possibility that two discrete regions of deletion at 7q22 are involved in the development of a subset of leiomyomas. Genes Chromosom. Cancer 19:156–160, 1997. © 1997 Wiley‐Liss Inc.

7q deletion mapping and expression profiling in uterine fibroids

“…Also, the lack of chromosomal deletions in two tumours showing LOH indicates that mitotic recombination, rather than deletion, may be the cause of LOH in some fibroids (Gupta et al, 1997;Blackburn et al, 2004). Since the previous deletion mapping efforts on fibroids were conducted before the final version of the human genetic map was available, some of the marker information has changed (Ishwad et al, 1995(Ishwad et al, , 1997van der Heijden et al, 1998;Mao et al, 1999). In particular, the results by van der Heijden et al rely critically on marker D7S501, the published reverse primer of which does not have a perfect match on the 7q22.3 target region in the latest version (v29.35b) of Ensembl (www.ensembl.org) genome browser, thus making the assessment of LOH in our experience nonreproducible (data not shown).…”

“…In particular, the results by van der Heijden et al rely critically on marker D7S501, the published reverse primer of which does not have a perfect match on the 7q22.3 target region in the latest version (v29.35b) of Ensembl (www.ensembl.org) genome browser, thus making the assessment of LOH in our experience nonreproducible (data not shown). When this and the possibility of a small homozygous deletion as the explanation for retention of heterozygosity (Cairns et al, 1994;Ishwad et al, 1997) are taken into account, the former smallest commonly deleted region was 5.3 Mb and flanked by markers D7S518 and D7S496. Our data further reduces the commonly deleted region to be flanked by markers 7qAC005070 and D7S496, a region of only 2.3 Mb.…”

“…The most common alterations have been deletions on chromosome 7q21-q31, and other abnormalities have involved chromosomes 6, 12 and 14 (Nibert and Heim, 1990). In addition, several allelotyping studies of uterine fibroids have discovered deletions on chromosome 7q21-q31 (Ishwad et al, 1995(Ishwad et al, , 1997van der Heijden et al, 1998;Mao et al, 1999). All these studies consistently point to a common deleted region around markers D7S518 and D7S471, which according to Knudson's two-hit model suggests a leiomyoma suppressor gene in that region.…”

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

“…5 Deletions on chromosome 7q, del(7q), were found in approximately 35% of cases with cytogenetic abnormalities (128/ 366), and the smallest commonly deleted region of 7q was mapped to band 7q22. 1,[7][8][9][10] The high proportion of cytogenetically detectable deletions of 7q22 in leiomyomas and other types of cancer suggests that a tumor-suppressor gene may be located within this chromosomal region. 1,9 We previously reported that CUTL1 was present in a commonly deleted region in 7/50 uterine leiomyoma samples examined.…”

Refined mapping of the region of loss of heterozygosity on the long arm of chromosome 7 in human breast cancer defines the location of a second tumor suppressor gene at 7q22 in the region of the CUTL1 gene

“…The region of LOH at 7q22 in every case included one or more of three polymorphic markers that are located within the CUTL1 gene. LOH of 7q22 has also been documented in the case of human uterine leiomyomas (Zeng et al, 1997;Ishwad et al, 1997). Interestingly, in both leiomyomas and mammary tumors induced in transgenic mice expressing the Polyomavirus (PyV) large T (LT) antigen, immunocomplexes of CUTL1 and PyV LT antigen were detected (Webster et al, 1998).…”